Neoplasia最新文献

{"title":"Generation of orthotopic intracranial glioblastoma patient-derived xenograft models: insights into extrachromosomal DNA-driven MYC(N) and PDGFRA oncogene amplification and preliminary therapeutic evaluation","authors":"Thi-Anh-Thuy Tran ,&nbsp;Sinae An ,&nbsp;Junghyun Lim ,&nbsp;Young-Hee Kim ,&nbsp;Ahyeon Shim ,&nbsp;Taewoo Han ,&nbsp;Hawsan Kim ,&nbsp;Sue-Jee Park ,&nbsp;Yeong Jin Kim ,&nbsp;Kyung-Sub Moon ,&nbsp;In-Young Kim ,&nbsp;Shin Jung ,&nbsp;Chul Won Lee ,&nbsp;Kyung-Hwa Lee ,&nbsp;Ae Kyung Park ,&nbsp;Tae-Young Jung","doi":"10.1016/j.neo.2025.101233","DOIUrl":"10.1016/j.neo.2025.101233","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to establish orthotopic intracranial patient-derived xenograft (PDX) models to investigate molecular and pathological features and to evaluate potential preclinical therapeutic approaches in glioblastoma (GBM).</div></div><div><h3>Methods</h3><div>Fresh or cryopreserved patient tumor tissues were first expanded as subcutaneous PDXs and subsequently used to generate orthotopic intracranial PDXs. Tumor growth and similarity to patient tumors were assessed by magnetic resonance imaging (MRI), pathological analyses, and multi-omics profiling. A selected intracranial PDX was further used to evaluate the potential preclinical efficacy of natural killer (NK) cells combined with Avastin® and irinotecan. The cytotoxic effects of this combination were also examined in primary GBM cells obtained from the original tumor of the same PDX.</div></div><div><h3>Results</h3><div>Subcutaneous PDX engraftment was successful in 13 out of 16 cases (81.3 %), and orthotopic intracranial PDXs were established from six of these with a 100 % success rate. Subcutaneous tumors expanded within 9 to 31 weeks, while intracranial tumors formed within 4 to 14 weeks. Subcutaneous growth was influenced by the Ki-67 index and the cryopreservation duration. Multi-omics analysis revealed extrachromosomal DNA (ecDNA)-driven amplifications of MYC(N), PDGFRA, CDK4, and MDM2 in PDXs from two patients. PDGFRA, CDK4, and MDM2 amplifications were consistent with those in the primary tumors, whereas MYC(N) amplification, initially minimal or absent in patient samples, was markedly enriched in the PDXs. Of the multiple PDXs from a single patient, the one PDX harboring ecDNA-driven MYCN amplification showed a greatly accelerated growth rate. Notably, PDXs containing ecDNA-driven MYC amplification exhibited a histological transformation toward primitive embryonal features. Combining NK cells with Avastin® and irinotecan enhanced cytotoxicity in vitro and prolonged survival in intracranial PDXs harboring ecDNA-driven MYC and PDGFRA amplifications.</div></div><div><h3>Conclusion</h3><div>Intracranial PDX models were successfully established from cryopreserved GBM tissues through subcutaneous expansion. These models offer a clinically relevant platform for investigating GBM biology and evaluating the therapeutic efficacy of chemoimmunotherapy.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101233"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting lysosomal protease CTSL promotes anti-tumor immunity and sensitizes HNSCC to PD-1 blockade by stabilizing PDK1 and activating Akt–PD-L1 axis","authors":"Yaodong Ding ,&nbsp;Haoyu Zhang ,&nbsp;Xueying Wang ,&nbsp;Jiaqi Tan ,&nbsp;Minghao Wang ,&nbsp;Yuhan Chen ,&nbsp;Imadoudini Hassimi Safia ,&nbsp;Gangcai Zhu ,&nbsp;Xin Zhang ,&nbsp;Yong Liu","doi":"10.1016/j.neo.2025.101228","DOIUrl":"10.1016/j.neo.2025.101228","url":null,"abstract":"<div><div>Cathepsin L (CTSL) is expressed in head and neck squamous cell carcinoma (HNSCC), yet its role in immune escape is unclear. Here we show that CTSL directly binds PDK1, blocks its ubiquitin and restrains NEDD4L-mediated ubiquitination, thereby stabilizing PDK1, sustaining AKT phosphorylation, and increasing PD-L1 on tumor cells. This establishes a non-proteolytic scaffolding function, and suppresses tumor growth in xenograft and immunocompetent mouse models; these effects synergize with anti-PD-1 therapy. Clinically, high CTSL expression correlates with increased PD-L1, scarce CD8+ <em>T</em>-cell infiltration, and poor prognosis in multiple HNSCC cohorts. Collectively, our data identify CTSL as a key driver of PD-L1-dependent immune evasion through the CTSL–PDK1–AKT axis and highlight CTSL inhibition as a promising therapeutic strategy and predictive biomarker for PD-1/PD-L1 blockade in HNSCC.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101228"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GBP1-CDK9-STAT3 signaling axis promotes osteosarcoma PD-L1 expression and immune escape","authors":"Doudou Jing ,&nbsp;Binghong Chen ,&nbsp;Ruqi Liang ,&nbsp;Fei Li ,&nbsp;Bin Zhao ,&nbsp;Feifei Pu ,&nbsp;Wei Wu","doi":"10.1016/j.neo.2025.101232","DOIUrl":"10.1016/j.neo.2025.101232","url":null,"abstract":"<div><div>Osteosarcoma is a common malignant bone tumor, characterized by its high invasiveness and propensity for lung metastasis. Despite advances in treatment, clinical outcomes remain poor, and patient prognosis is still unsatisfactory. Therefore, the development of more effective therapies is urgently needed. Here, we demonstrate that differential expression of GBP1 significantly influences PD-L1 expression and mediates immune escape in osteosarcoma. Specifically, our results reveal that GBP1 regulates PD-L1 expression by activating CDK9 and promoting STAT3 phosphorylation. These findings suggest that targeting GBP1 may represent a promising therapeutic strategy for the treatment of osteosarcoma by impairing tumor immune evasion.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101232"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of the immune bone marrow microenvironment to tumor growth and bone deconstruction: implications for improving immunotherapeutic strategies in bone metastasis","authors":"E. Massy ,&nbsp;C.B. Confavreux ,&nbsp;M. Point ,&nbsp;E. Bonnelye ,&nbsp;P. Clézardin","doi":"10.1016/j.neo.2025.101224","DOIUrl":"10.1016/j.neo.2025.101224","url":null,"abstract":"<div><div>Bone metastases are frequent complications of many solid tumors, leading to painful skeletal morbidities and increasing mortality for patients with advanced cancer. Once in bone, cancer cells deregulate bone homeostasis, altering the functions of bone-forming (osteoblasts) and bone-resorbing (osteoclasts) cells, which results in skeletal deconstruction. Aside from bone cells, cancer cells in the bone marrow interact with other cell populations, including immune cells that also play an integral part in the regulation of bone homeostasis. In this respect, immune checkpoint inhibitors (ICIs) have become a standard of care in immunotherapy for the treatment of patients with advanced cancer. Strikingly, however, those with bone metastases have a shorter survival when treated with ICIs than ICI-treated cancer patients without bone metastases. In this Review, after presenting the immune cells involved in bone metastasis, we review preclinical and clinical findings assessing ICI efficacy both in bone and extraosseous metastases, and we discuss the clinical utility of using bone-targeted agents —including denosumab and bisphosphonates— to improve anti-tumoral efficacy of ICI treatments in patients with cancer and bone metastases.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101224"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A spatiotemporal atlas of orchiectomy-induced androgen deprivation-mediated modulation of cellular composition and gene expression in the mouse prostate","authors":"Greg Shelley ,&nbsp;Allison May ,&nbsp;Tyler Robinson ,&nbsp;Jinlu Dai ,&nbsp;Sethu Pitchiaya ,&nbsp;Evan T. Keller","doi":"10.1016/j.neo.2025.101230","DOIUrl":"10.1016/j.neo.2025.101230","url":null,"abstract":"<div><div>Androgen deprivation therapy (ADT) remains a cornerstone in the treatment of prostate cancer (PCa), yet most tumors eventually develop resistance. Murine models are widely used to study PCa progression and ADT response, but a detailed understanding of the prostate’s biological response to androgen deprivation in these models is lacking. Here, we present a spatiotemporal analysis of cellular and transcriptional dynamics in the mouse prostate following orchiectomy (ORX)-induced androgen deprivation with a focus on non-epithelial components. We observed progressive involution across all prostate lobes (dorsal, ventral, lateral, and anterior) and distinct lobe-specific temporal gene expression changes post-ORX. Immune cell infiltration markedly increased over time, highlighting a shift in the prostate’s cellular landscape. Single-cell RNA sequencing uncovered a previously undescribed fibroblast subtype—termed ORX-induced fibroblast (OIF)—characterized by high expression of Wnt2, Rorb, and Wif1, with distinct spatial localization. Pathway analysis revealed upregulation of amide and peptide binding functions, alongside suppression of peptidase and endopeptidase activity. Furthermore, dynamic changes in ligand–receptor interactions across lobes underscored the evolving intercellular communication in the post-ORX prostate. By integrating spatial transcriptomics with single-cell profiling, our study generates a high-resolution atlas of the murine prostate’s response to androgen deprivation. These findings provide a foundational resource for interpreting ADT responses in preclinical models of PCa.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101230"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAM111B enhances glycolysis and promotes metastasis of prostate cancer by upregulating LDHA","authors":"Qingliu He ,&nbsp;Haoran Li ,&nbsp;Yukun Cong ,&nbsp;Kang Chen ,&nbsp;Lulin Cheng ,&nbsp;Fang Lv ,&nbsp;Pu Zhang ,&nbsp;Yunjie Ju ,&nbsp;Zehao Yu ,&nbsp;Jinyu Chen ,&nbsp;Chuxiong Wang ,&nbsp;Yarong Song ,&nbsp;Xuechao Li ,&nbsp;Liang Chen ,&nbsp;Yifei Xing","doi":"10.1016/j.neo.2025.101227","DOIUrl":"10.1016/j.neo.2025.101227","url":null,"abstract":"<div><h3>Background</h3><div>The poor prognosis of metastatic prostate cancer (PCa) poses a major burden on both patients and the healthcare system. FAM111 trypsin-like peptidase B (FAM111B) is related to the development and progression of a wide array of cancers, but its role in PCa remains poorly understood.</div></div><div><h3>Methods</h3><div>Primary cells were extracted from subcutaneous and pulmonary metastatic tumors and were used to verify differences in metastatic potential through wound healing assay, Transwell assay, soft agar colony formation assay, and in vivo pulmonary metastasis reformation assays. The key differentially expressed gene FAM111B related to metastatic prostate cancer (mPCa) was identified through transcriptomic combination analysis, proteomic analysis, quantitative real-time fluorescent polymerase chain reaction and western blot assays. The effect of FAM111B on the glycolytic capacity of PCa cells with high metastatic potential was analyzed by gene enrichment analysis, glucose uptake, lactate and ATP content measurement assays, including glycolytic stress test.</div></div><div><h3>Results</h3><div>FAM111B was highly expressed in metastatic PCa cells and associated with adverse clinical features, which upregulated LDHA to enhance glycolysis. Mechanistically, the expression of P27 was inhibited by a hydrolytic triad coded by the functional coding region of FAM111B, which activated Cyclin-CDKs/RB/E2F1 classical signaling pathway to promote the transcription and protein expression of LDHA.</div></div><div><h3>Conclusions</h3><div>The high expression of FAM111B is associated with adverse clinical features of PCa. FAM111B protein binds to and hydrolyzes P27 protein, which activates Cyclin-CDKs/RB/E2F1 signaling pathway to increase LDHA expression, thereby enhancing the glycolytic ability and ultimately promoting the metastasis of PCa and may potentially serve as new targets for the treatment of metastatic PCa.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"69 ","pages":"Article 101227"},"PeriodicalIF":7.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition","authors":"Zofia M. Komar ,&nbsp;Mieke Bavelaar ,&nbsp;Ellen Kageler ,&nbsp;Nicole S. Verkaik ,&nbsp;Mandy M. van Rosmalen ,&nbsp;Carolien H.M. van Deurzen ,&nbsp;Michael A. den Bakker ,&nbsp;Roland Kanaar ,&nbsp;Adriaan B Houtsmuller ,&nbsp;Thierry P.P. van den Bosch ,&nbsp;Agnes Jager ,&nbsp;Dik C. van Gent","doi":"10.1016/j.neo.2025.101221","DOIUrl":"10.1016/j.neo.2025.101221","url":null,"abstract":"<div><div>Personalized medicine for breast cancer (BrC) requires predictive biomarkers to select the optimal therapeutic option for each individual patient. Personalization of chemotherapy or immunotherapy responses is particularly challenging, as molecular markers do not appear to be sufficiently predictive for therapy response. Functional assays for therapy selection may be the solution for this dilemma. An interesting approach is <em>ex vivo</em> cultures of precision cut tumor slices, such as the MOtion-based Tissue EX vivo (MOTEX) method that we described previously. This culture method has the advantage that it carries all cell types in the tumor, including various immune cell populations. We here show, that macrophages, B-cells and T-cell populations are maintained in the MOTEX culture for several days without apparent loss of viability. Even treatment with the microtubule poison paclitaxel did not reduce immune cell abundance or viability significantly. Anthracycline-based chemotherapy, however, did affect immune cell composition, as expected based on its cytotoxic properties. Therefore, we conclude that MOTEX culture of BrC tissue slices can be used to investigate effect of treatments that involve the immune system. This opens perspectives to develop predictive assays for immune checkpoint inhibitor treatment and other therapeutic interventions that require immune components in the assay system.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"68 ","pages":"Article 101221"},"PeriodicalIF":7.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An effective multistage mouse model of esophageal carcinogenesis for preclinical and computational pathology applications","authors":"Yuxia Fu ,&nbsp;Guoqing Zhang ,&nbsp;Yue Liu ,&nbsp;Lei Xu ,&nbsp;Yuanyuan Hu ,&nbsp;Liyan Xue ,&nbsp;Huiqin Guo ,&nbsp;Yan Fu ,&nbsp;Yigang Cen ,&nbsp;Xiao Li ,&nbsp;Wei Jiang ,&nbsp;Xiying Yu","doi":"10.1016/j.neo.2025.101217","DOIUrl":"10.1016/j.neo.2025.101217","url":null,"abstract":"<div><div>The use of <em>c</em>arcinogen-<em>i</em>nduced <em>m</em>ultistage <em>c</em>arcinogenesis animal <em>m</em>odels of esophageal squamous cell carcinoma (CIMCM of ESCC) is limited by prolonged timelines, high toxicity, and excessive mutational burden. In this study, we report the establishment of an effective mouse CIMCM of ESCC by using 4-nitroquinoline-1-oxide (4NQO) as a carcinogen and sorafenib (SOR) as a tumor promoter. We show that SOR specifically activates the Raf-MEK-ERK signaling pathway in normal esophageal stratified squamous epithelium cells, thereby promoting tumor progression. This CIMCM of ESCC accurately recapitulates the multistage process of ESCC carcinogenesis from precancerous lesions to invasive carcinoma, with shortened time and high efficiency. Pathological, molecular, cellular and multiomic analyses show that the CIMCM of ESCC significantly reduces the tumor mutation burden to levels detected in human ESCC samples, while preserving key genetic driver mutations and abnormal transcriptomic/protein expression profiles. Notably, the CIMCM of ESCC demonstrates that the tissue microenvironment plays an important role in ESCC carcinogenesis, as the application of mechanical injury to the esophageal SSE of the CIMCM results in the inflammatory-related response, site-specific tumor formation and high tumor incidence. Since the CIMCM of ESCC provides valuable samples from different stages of tumor initiation and progression, the pathological whole slide images of the CIMCM of ESCC are applied to the computational pathology, which enables the detection, segmentation and annotation of the ESCC initiation and progression with pathologist-level accuracy. Taken together, this mouse CIMCM of ESCC provides a versatile platform for ESCC early diagnosis, basic and preclinical research and therapeutic strategy.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"68 ","pages":"Article 101217"},"PeriodicalIF":7.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropilin-2 upregulation by stromal TGFβ1 induces lung disseminated tumor cells dormancy escape and promotes metastasis outgrowth","authors":"L Recalde-Percaz ,&nbsp;I de la Guia-Lopez ,&nbsp;P Linzoain-Agos ,&nbsp;A Noguera-Castells ,&nbsp;M Rodrigo-Faus ,&nbsp;P Jauregui ,&nbsp;A Lopez-Plana ,&nbsp;P Fernández-Nogueira ,&nbsp;M Iniesta-González ,&nbsp;M Cueto-Remacha ,&nbsp;S Manzano ,&nbsp;R Alonso ,&nbsp;N Moragas ,&nbsp;C Baquero ,&nbsp;N Palao ,&nbsp;E Dalla ,&nbsp;FX Avilés-Jurado ,&nbsp;I Vilaseca ,&nbsp;X León-Vintró ,&nbsp;M Camacho ,&nbsp;P Bragado","doi":"10.1016/j.neo.2025.101220","DOIUrl":"10.1016/j.neo.2025.101220","url":null,"abstract":"<div><div>Metastasis is the main cause of death from solid tumors. Therefore, identifying the mechanisms that govern metastatic growth poses a major biomedical challenge. Tumor microenvironment signals regulate the fate and survival of disseminated tumor cells (DTCs) in secondary organs. However, very little is known about the role of nervous system mediators in this process. We have previously reported that neuropilin-2 (NRP2) expression in breast cancer correlates with poor prognosis. Here, we show that NRP2 positively regulates the proliferation, invasion, and survival of breast and head and neck cancer cells <em>in vitro</em>. NRP2 deletion in tumor cells inhibits tumor growth <em>in vivo</em> and decreases the number and size of lung metastases by promoting lung DTCs quiescence. NRP2 deletion upregulates dormancy and cell cycle regulators expression and promotes DTCs reprograming into quiescence. Moreover, lung fibroblasts and macrophages induce NRP2 upregulation in DTCs through the secretion of TGFβ1. NRP2 facilitates lung DTC interaction with the extracellular matrix and promotes lung DTCs activation and metastasis. Therefore, we conclude that the TGFβ1-NRP2 axis is a new key dormancy-awakening inducer that promotes DTCs proliferation and lung metastasis development.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"68 ","pages":"Article 101220"},"PeriodicalIF":7.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disitamab vedotin combined with toripalimab and radiotherapy for multimodal organ-sparing treatment of muscle invasive bladder cancer: a proof-of-concept study","authors":"Lu Zhang ,&nbsp;Di Jin ,&nbsp;Jingyu Zang ,&nbsp;Lei Qian ,&nbsp;Tianxiang Zhang ,&nbsp;Yuchen Wu ,&nbsp;Yu Ding ,&nbsp;Feng Xie ,&nbsp;Haoran Tang ,&nbsp;Jun Xia ,&nbsp;Dengfeng Cao ,&nbsp;Ruiyun Zhang ,&nbsp;Guanglei Zhuang ,&nbsp;Haige Chen","doi":"10.1016/j.neo.2025.101216","DOIUrl":"10.1016/j.neo.2025.101216","url":null,"abstract":"<div><h3>Purpose</h3><div>Although trimodal therapy is currently the standard organ-sparing approach for muscle-invasive bladder cancer (MIBC), its clinical benefit is limited, and noninvasive biomarkers to guide dynamic decision-making are lacking. Here, we present a proof-of-concept study evaluating disitamab vedotin (RC48, a HER2-targeted antibody-drug conjugate) combined with toripalimab (JS001, anti-PD-1) and radiotherapy for bladder preservation in localized HER2-positive MIBC.</div></div><div><h3>Patients and Methods</h3><div>In the first-stage of an open-label phase II clinical trial (ClinicalTrials.gov identifier: NCT05979740), six patients were enrolled and received disitamab vedotin, toripalimab, and radiotherapy. Adverse events were documented according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5.0). Tumor response was evaluated every 12 weeks by radiographic imaging, cystoscopy with biopsies, and urine cytology. In parallel, we performed longitudinal liquid biopsy analyses of circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) using PredicineCARE assay.</div></div><div><h3>Results</h3><div>The combination was overall tolerable, with no grade 4 treatment-related adverse events or deaths. Five patients (83.3 %) achieved a complete response and remained recurrence-free. Notably, utDNA testing showed high accuracy in monitoring therapeutic effectiveness and enabled early detection of tumor relapse, whereas ctDNA was largely undetectable across blood samples.</div></div><div><h3>Conclusions</h3><div>These findings establish the feasibility, efficacy, and potential biomarker utility of a novel bladder-preserving regimen, setting the stage for a paradigm shift in MIBC management.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"68 ","pages":"Article 101216"},"PeriodicalIF":7.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}